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  • Title: Two antiestrogens affect differently chromatin remodeling of trefoil factor 1 (pS2) gene and the fate of estrogen receptor in MCF7 cells.
    Author: Giamarchi C, Chailleux C, Calligé M, Rochaix P, Trouche D, Richard-Foy H.
    Journal: Biochim Biophys Acta; 2002 Oct 11; 1578(1-3):12-20. PubMed ID: 12393183.
    Abstract:
    We show here that the two antagonists ICI 182 780, a pure estrogen antagonist, and 4-hydroxy-tamoxifen, a selective estrogen receptor modulator (SERM) have distinct effects on TFF1 (formerly pS2) gene chromatin structure and transcription. Indeed, ICI 182 780 decreased both the intensity of the hormone-dependent DNase I hypersensitive site pS2 HS-1 and transcription of the pS2 gene whereas 4-hydroxy-tamoxifen (OH-Tam) increased the intensity of pS2-HS1 and had no effect on pS2 gene transcription. Interestingly, these differential effects are associated with different fates of ERalpha following the two treatments: The ERalpha-OH-Tam complex was retained in the nucleus more efficiently than the ERalpha-estradiol complex. In contrast, ICI 182 780 provoked a rapid relocation of ERalpha complex to an insoluble nuclear fraction, followed by its degradation. Taken together, these data suggest that regulating the amount of ERalpha in the nucleus is a major way of action of estrogen antagonists with respect to chromatin remodeling and transcriptional control.
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